Human T-cell lymphoma/leukemia virus (HTLV) is the etiological agent of adult T-cell lymphoma (ATL). Over10-20 million
people are infected with HTLV, which is endemic in regions of Japan, the Caribbean, South America, and Africa. ATL is
characterized by a monoclonal or oligoclonal expansion of T cells, allowing persistent proliferation of infected ATL cells. Telomerase, a reverse transcriptase, is able to extend the ends of DNA, allowing repetitive cycles of expansion, in the absence of a loss of DNA. We examined telomerase and its activity in in vitro HTLV cell lines and in vivo, in asymptomatic (AS) and ATL carriers. We found telomerase activity to be increased in ATL patients when compared to AS. However, despite the increase in telomerase expression and activity, telomere lengths remained short, when compared to AS carriers. To further investigate this seeming contradiction, we examined the levels of expression of telomere length regulators, TRF1,
TRF2, TIN2, and POT1, known to negatively regulate and control telomere lengths. While no increase in POT1 expression
was noted, a significant increase in TRF1 and TIN2, along with a smaller increase in TRF2 was found, demonstrating that while telomerase activity is high in ATL patients, telomerase may not be able to access the telomeric ends due to the binding of these regulators. Access to the telomeric ends may then be impaired due to the negative action of TRF1, TRF2, and
TIN2 in ATL patients, which allows for the maintenance of short telomeres in the absence of cellular senescence or
apoptosis.